Purpose: K-MASTER project is a Korean national precision medicine platform that screened actionable mutations by analyzing next-generation sequencing (NGS) of solid tumor patients. We compared gene analyses between NGS panel from the K-MASTER project and orthogonal methods. Materials and Methods: Colorectal, breast, non–small cell lung, and gastric cancer patients were included. We compared NGS results from K-MASTER projects with those of non-NGS orthogonal methods (KRAS, NRAS, and BRAF mutations in colorectal cancer [CRC]; epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK] fusion, and reactive oxygen species 1 [ROS1] fusion in non–small cell lung cancer [NSCLC], and Erb-B2 receptor tyrosine kinase 2 (ERBB2) positivity in breast and gastric cancers). Results: In the CRC cohort (n=225), the sensitivity and specificity of NGS were 87.4% and 79.3% (KRAS); 88.9% and 98.9% (NRAS); and 77.8% and 100.0% (BRAF), respectively. In the NSCLC cohort (n=109), the sensitivity and specificity of NGS for EGFR were 86.2% and 97.5%, respectively. The concordance rate for ALK fusion was 100%, but ROS1 fusion was positive in only one of three cases that were positive in orthogonal tests. In the breast cancer cohort (n=260), ERBB2 amplification was detected in 45 by NGS. Compared with orthogonal methods that integrated immunohistochemistry and in situ hybridization, sensitivity and specificity were 53.7% and 99.4%, respectively. In the gastric cancer cohort (n=64), ERBB2 amplification was detected in six by NGS. Compared with orthogonal methods, sensitivity and specificity were 62.5% and 98.2%, respectively. Conclusion The results of the K-MASTER NGS panel and orthogonal methods showed a different degree of agreement for each genetic alteration, but generally showed a high agreement rate.

Purpose: The purpose of this study was to identify the concordant or discordant genomic profiling between primary and matched metastatic tumors in patients with colorectal cancer (CRC) and to explore the clinical implication. Materials and Methods: Surgical samples of primary and matched metastatic tissues from 158 patients (335 samples) with CRC at Korea University Anam Hospital were evaluated using the Ion AmpliSeq Cancer Hotspot Panel. We compared genetic variants and classified them as concordant, primary-specific, and metastasis-specific variants. We used a combination of principal components analysis and clustering to find genomic groups. Kaplan-Meier curves were used to appraise survival between genomic groups. We used machine learning to confirm the correlation between genetic variants and metastatic sites. Results: A total of 282 types of deleterious non-synonymous variants were selected for analysis. Of a total of 897 variants, an average of 40% was discordant. Three genomic groups were yielded based on the genomic discrepancy patterns. Overall survival differed significantly between the genomic groups. The poorest group had the highest proportion of concordant KRAS G12V and additional metastasis-specific SMAD4. Correlation analysis between genetic variants and metastatic sites suggested that concordant KRAS mutations would have more disseminated metastases. Conclusion Driver gene mutations were mostly concordant; however, discordant or metastasis-specific mutations were present. Clinically, the concordant driver genetic changes with additional metastasis-specific variants can predict poor prognosis for patients with CRC.

PURPOSE: To compare the surgical outcomes between trabeculectomy with a collagen matrix (Ologen®) insertion and conventional trabeculectomy. METHODS: An ophthalmic examination, including tonometry and a slit lamp examination, was performed 1 week, 2 weeks, 1 month, 2 months, 4 months, 6 months, and 12 months postoperatively in glaucoma patients who underwent a trabeculectomy using Ologen® (experimental group) or a conventional trabeculectomy (control group). Clinical features including success rate and complications were compared between the two groups. RESULTS: In 21 eyes of the experimental group and 42 eyes of the control group, the success rates were 76% and 69%, respectively (p = 0.554). Needling with subconjunctival 5-fluorouracil injection or laser suture lysis of the scleral flap was required in three eyes (14.3%) in the experimental group and 18 eyes (42.9%) in the control group (p = 0.023). The types of complications differed, although the total number of complications did not differ between the two groups (23.8% vs. 19.0%, respectively; p = 0.745). The most common complication in the experimental group was an encapsulated bleb, which occurred in three eyes (14.3%), whereas an avascular bleb occurred in three eyes (7.1%) in the control group. CONCLUSIONS: The success rate of trabeculectomy with Ologen® was comparable to that of conventional trabeculectomy. However, postoperative interventions were less commonly required after trabeculectomy with Ologen®, and the complications differed between the groups. When choosing the surgical method and examining the postoperative condition, these differences should be considered.
Blister ; Collagen ; Fluorouracil ; Glaucoma ; Humans ; Manometry ; Methods ; Slit Lamp ; Sutures ; Trabeculectomy

PURPOSE: To evaluate the therapeutic effect of human embryonic stem cell (hESC)-derived multipotent mesenchymal stem cells (M-MSCs) on ketamine-induced cystitis (KC) in rats. METHODS: To induce KC, 10-week-old female rats were injected with 25-mg/kg ketamine hydrochloride twice weekly for 12 weeks. In the sham group, phosphate buffered saline (PBS) was injected instead of ketamine. One week after the final injection of ketamine, the indicated doses (0.25, 0.5, and 1×106 cells) of M-MSCs (KC+M-MSC group) or PBS vehicle (KC group) were directly injected into the bladder wall. One week after M-MSC injection, the therapeutic outcomes were evaluated via cystometry, histological analyses, and measurement of gene expression. Next, we compared the efficacy of M-MSCs at a low dose (1×105 cells) to that of an identical dose of adult bone marrow (BM)-derived MSCs. RESULTS: Rats in the KC group exhibited increased voiding frequency and reduced bladder capacity compared to rats of the sham group. However, these parameters recovered after transplantation of M-MSCs at all doses tested. KC bladders exhibited markedly increased mast cell infiltration, apoptosis, and tissue fibrosis. Administration of M-MSCs significantly reversed these characteristic histological alterations. Gene expression analyses indicated that several genes associated with tissue fibrosis were markedly upregulated in KC bladders. However the expression of these genes was significantly suppressed by the administration of M-MSCs. Importantly, M-MSCs ameliorated bladder deterioration in KC rats after injection of a low dose (1×105) of cells, at which point BM-derived MSCs did not substantially improve bladder function. CONCLUSIONS: This study demonstrates for the first time the therapeutic efficacy of hESC-derived M-MSCs on KC in rats. M-MSCs restored bladder function more effectively than did BM-derived MSCs, protecting against abnormal changes including mast cell infiltration, apoptosis and fibrotic damage.
Adult ; Animals ; Apoptosis ; Bone Marrow ; Cystitis ; Female ; Fibrosis ; Gene Expression ; Human Embryonic Stem Cells ; Humans ; Ketamine ; Mast Cells ; Mesenchymal Stromal Cells ; Multipotent Stem Cells ; Pelvic Pain ; Rats ; Urinary Bladder

PURPOSE: We report a case of Parry-Romberg syndrome associated with right enophthalmos, hypotropia, up-gaze limitation, en coup the sabre, morphea, and hypothyroidism. CASE SUMMARY: A 41-year-old woman presented with slowly progressive right enophthalmos that started 5 years previous. With a Hertel exophthalmometer, the right eye measured 10 mm, and the left eye 13 mm. Right enophthalmos and atrophy of subcutaneous tissues of right side orbit were observed. Axial scan of computerized tomography shows atrophy of right side orbital subcutaneous tissues without bony abnormality. At primary gaze, 4 prism diopter hypotropia was observed in the right eye. Up-gaze was limited in both eyes. Visual acuity was 1.0 in both eyes. No specific sign was found in her anterior segment. The patient had experienced right side alopecia 20 years prior and had undergone biopsy, which proved morphea. Linear en coup de sabre morphea was found on the right forehead and scalp. Hypothyroidism due to Hashimoto's thyroiditis was diagnosed based on a blood test, which also showed positive antinuclear antibody. Thus, the patient was diagnosed with Parry-Romberg syndrome associated with hypothyroidism. CONCLUSIONS: Clinicians need to consider the rare disease Parry-Romberg syndrome when a patient with ophthalmologic symptoms such as enopthlamos or eye movement disorders is accompanied by dermatologic symptoms such as linear en coup de sabre morphea or alopecia.
Adult ; Alopecia ; Antibodies, Antinuclear ; Atrophy ; Biopsy ; Enophthalmos ; Facial Hemiatrophy* ; Female ; Forehead ; Hematologic Tests ; Humans ; Hypothyroidism* ; Ocular Motility Disorders ; Orbit ; Rare Diseases ; Scalp ; Scleroderma, Localized ; Subcutaneous Tissue ; Thyroid Gland ; Thyroiditis ; Visual Acuity

OBJECTIVE: Hemodialysis patients may have psychological distress and reduced quality of life (QoL) related to chronic physical health problems. Genetic polymorphisms associated with reduced QoL in hemodialysis patients. The aim of this study was to investigate the relationship between genetic polymorphisms and variation in health-related QoL in Korean hemodialysis patients. METHODS: The 36-item Short-Form Health Survey and the Korean Hospital Anxiety and Depression Scale were used to assess health-related QoL and psychological distress, respectively. Twenty hundred and five clinically stable patients from 6 hemodialysis centers have participated with informed consents. Sociodemographic factors, clinical factors, and genotypes of serotonin 1A receptor, brain-derived neurotrophic factors, and glucocorticoid receptor were assessed. Independent t-tests, correlation analyses, multiple regression analyses were performed for statistical analyses. RESULTS: The serotonin 1A receptor CC genotype group showed significantly higher physical and mental QoL levels than those with the GG/GC genotypes. In the final linear regression analysis, serotonin 1A receptor CC genotype was significantly associated with positive physical and mental QoL levels. CONCLUSION: ConclusionaaSerotonin 1A receptor polymorphism, as well as age and depression, were significantly associated with mental and physical QoL in hemodialysis patients. Functional activity in the serotonin receptor system may have a modulating effect on health-related QoL in hemodialysis patients.
Anxiety ; Brain-Derived Neurotrophic Factor ; Depression ; Genotype ; Health Surveys ; Humans ; Linear Models ; Polymorphism, Genetic ; Quality of Life* ; Receptor, Serotonin, 5-HT1A* ; Receptors, Glucocorticoid ; Renal Dialysis* ; Serotonin*

Recepteur d'origine nantais (RON) is a receptor tyrosine kinase belonging to the subfamily of which c-MET is the prototype. Large epidemiologic studies have confirmed the strong association between RON and gastric cancer development. Constitutive activation of RON signaling directly correlates with tumorigenic phenotypes of gastric cancer and a poor survival rate in advanced gastric cancer patients. In this review, we focus on recent evidence of the aberrant expression and activation of RON in gastric cancer tumors and provide insights into the mechanism of RON signaling associated with gastric cancer progression and metastasis. Current therapeutics against RON in gastric cancer are summarized.
Epidemiologic Studies ; Humans ; Neoplasm Metastasis ; Phenotype ; Protein-Tyrosine Kinases ; Proto-Oncogene Proteins c-met ; Stomach Neoplasms ; Survival Rate

PURPOSE: To evaluate the significance of axial length, which is a known risk factor of retinal vein occlusion, we measured the axial lengthby using contact A-scan sonography and partial interferometry and compared the two values. METHODS: This study included 19 patients complaining of visual symptoms and who were diagnosed with unilateral retinal vein occlusion (RVO) with macular edema (ME). Affected eyes were classified as the study group, and healthy fellow eyes were classified as the control group. We measured the central macular thickness (CMT) and axial length (AL) of the affected and fellow eyes and compared them. CMT was measured by optical coherence tomography (Stratus OCT, Carl Zeiss, Jena, Germany), and AL was measured by interferometry (IOL Master®, Carl Zeiss, Jena, Germany). RESULTS: In RVO patients, CMT was significantly different between affected eyes (485.7 ± 111.3 µm) and fellow eyes (197.8 ± 29.7 µm; p < 0.001). Axial length measured by A-scan sonography was 23.06 ± 0.86 mm in the affected eyes and 23.28 ± 0.93 mm in the healthy eyes, which was statistically different (p < 0.001). However, using partial interferometry, the AL was 23.35 ± 0.87 mm in the affected eyes and 23.38 ± 0.95 mm in the healthy eyes. No significant difference was found. CONCLUSIONS: We confirmed that short AL, which was once thought to be a risk factor of RVO, results from the properties of the instruments used for measurement. Moreover, we verified that partial interferometry is more accurate for measurement of AL than A-scan sonography when retinal vein occlusion is associated with ME.
Humans ; Interferometry* ; Macular Edema ; Retinal Vein Occlusion* ; Retinal Vein* ; Retinaldehyde* ; Risk Factors ; Tomography, Optical Coherence ; Ultrasonography*

Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm characterized by sustained neutrophilia, splenomegaly, and hypercellular bone marrow without Philadelphia chromosome. Diagnosis of CNL requires exclusion of identifiable causes of reactive neutrophilia, such as infection and tumors. Our patient presented with general weakness and weight loss. Computed tomography (CT) showed a mass in the distal rectum, which was confirmed to be an adenocarcinoma by colonoscopic biopsy. Positron emission tomography-CT showed multiple liver, bone, and lymph node metastases. Liver and lymph node biopsies revealed neutrophilic infiltration with no evidence of adenocarcinoma. The pathological findings of the bone marrow were compatible with CNL. Cytogenetic analysis revealed a normal karyotype, and molecular analysis was negative for BCR/ABL. Here, we present a 73 year-old man diagnosed with concurrent CNL and rectal cancer.
Adenocarcinoma ; Biopsy ; Bone Marrow ; Cytogenetic Analysis ; Diagnosis ; Electrons ; Humans ; Karyotype ; Leukemia ; Leukemia, Neutrophilic, Chronic* ; Leukemoid Reaction ; Leukocytosis ; Liver ; Lymph Nodes ; Neoplasm Metastasis ; Neutrophils ; Philadelphia Chromosome ; Rectal Neoplasms* ; Rectum ; Splenomegaly ; Weight Loss

PURPOSE: To report a case of Pseudomonas aeruginosa infection after scleral buckling for retinal detachment. CASE SUMMARY: A 68-year-old male presented with a 2-day history of pain in the right eye. The patient had a history of scleral buckling for retinal detachment 10 years earlier and excisional biopsy for conjunctival mass 1 month previously. Biopsy revealed chronic inflammation and granulation tissue formation. Slit-lamp examinations revealed superior conjunctival injection, edema and exposed suture knot. Fundus examination revealed exudative retinal detachment and choroidal detachment. The conjunctival lesion did not improve although the patient was treated with moxifloxacin. After 4 days, bacterial and fungal cultures were performed because the conjunctiva presented with purulent discharge 4 days after treatment. The scleral buckle and suture knot were removed. The cultures revealed growth of Pseudomonas aeruginosa. According to antibiotic sensitivity test results, the authors treated the patient with ceftazidime. The conjunctival lesion, choroidal detachment and exudative retinal detachment were improved. CONCLUSIONS: In patients with conjunctival injection, edema, purulent discharge and ocular pain after scleral buckling, presence of infection should be suspected. If scleral buckle infection is suspected, bacterial culture, antibiotics treatment and scleral buckle removal should be considered.
Aged ; Anti-Bacterial Agents ; Biopsy ; Ceftazidime ; Choroid ; Conjunctiva ; Edema ; Granulation Tissue ; Humans ; Inflammation ; Male ; Pseudomonas aeruginosa* ; Pseudomonas* ; Retinal Detachment* ; Retinaldehyde* ; Scleral Buckling* ; Sutures